Oral Exposure (oral + exposure)

Distribution by Scientific Domains


Selected Abstracts


Toxicity of trichloroethylene following inhalation and drinking contaminated water

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2001
Mohammad Waseem
Abstract The neurobehavioural effects of trichloroethylene (TCE) were studied in rats following administration of the solvent orally (350, 700 and 1400 ppm in drinking water for 90 days) and through inhalation (376 ppm for 4 h a day, 5 days per week for 180 days). Various aspects of spontaneous locomotor activity were assessed at different periods after exposure through either of the routes. Oral exposure to TCE had no significant effect on spontaneous locomotor activity or cognitive ability, whereas inhalation to the solvent resulted in an increase in the distance travelled and horizontal activity counts at day 30 but a decrease at day 60 of exposure. The time spent in ambulatory and stereotypic movements as well as the number of stereotypic movements were enhanced significantly only at day 30. The resting time was decreased at day 30 but enhanced at day 60 of exposure. The learning ability was not affected significantly up to day 180. The results highlight the neurotoxic potential of inhalation exposure to TCE. Copyright © 2001 John Wiley & Sons, Ltd. [source]


DNA adduct kinetics in reproductive tissues of DNA repair proficient and deficient male mice after oral exposure to benzo(a)pyrene

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2010
Nicole Verhofstad
Abstract Benzo(a)pyrene (B[a]P) can induce somatic mutations, whereas its potential to induce germ cell mutations is unclear. There is circumstantial evidence that paternal exposure to B[a]P can result in germ cell mutations. Since DNA adducts are thought to be a prerequisite for B[a]P induced mutations, we studied DNA adduct kinetics by 32P-postlabeling in sperm, testes and lung tissues of male mice after a single exposure to B[a]P (13 mg/kg bw, by gavage). To investigate DNA adduct formation at different stages of spermatogenesis, mice were sacrificed at Day 1, 4, 7, 10, 14, 21, 32, and 42 after exposure. In addition, DNA repair deficient (Xpc,/,) mice were used to study the contribution of nucleotide excision repair in DNA damage removal. DNA adducts were detectable with highest levels in lung followed by sperm and testis. Maximum adduct levels in the lung and testis were observed at Day 1 after exposure, while adduct levels in sperm reached maximum levels at ,1 week after exposure. Lung tissue and testis of Xpc,/, mice contained significantly higher DNA adduct levels compared to wild type (Wt) mice over the entire 42 day observation period (P < 0.05). Differences in adduct half-life between Xpc,/, and Wt mice were only observed in testis. In sperm, DNA adduct levels were significantly higher in Xpc,/, mice than in Wt mice only at Day 42 after exposure (P = 0.01). These results indicate that spermatogonia and testes are susceptible for the induction of DNA damage and rely on nucleotide excision repair for maintaining their genetic integrity. Environ. Mol. Mutagen. 2010. © 2009 Wiley-Liss, Inc. [source]


In vivo genotoxic effects of industrial waste leachates in mice following oral exposure

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 5 2006
Saurabh Chandra
Abstract Contamination of ground water by industrial waste poses potential health hazards for man and his environment. The improper disposal of toxic wastes could allow genotoxic chemicals to percolate into ground waters, and these contaminated ground waters may produce toxicity, including mutation and eventually cancer, in exposed individuals. In the present study, we evaluated the in vivo genotoxic potential of leachates made from three different kinds of industrial waste (tannery waste, metal-based waste, and waste containing dyes and pigments) that are disposed of in areas adjoining human habitation. Three different doses of test leachates were administered by oral gavage for 15 consecutive days to Swiss albino mice; their bone marrow cells were examined for chromosome aberrations (CAs), micronucleated polychromatic erythrocytes (MNPCEs), and DNA damage using the alkaline Comet assay. Exposure to the leachates resulted in significant (P < 0.05 or P < 0.001) dose-dependent increases in chromosome and DNA damage. Fragmented chromosomes and chromatid breaks were the major CAs observed. Chemical analysis of the leachates indicated that chromium and nickel were elevated above the limits established by health organizations. The highest levels of genotoxicity were produced by the metal-based leachate and the tannery-waste leachate, while the dye-waste leachate produced weaker genotoxic responses. The cytogenetic abnormalities and DNA damage produced by the leachates indicate that humans consuming water contaminated with these materials are at increased risk of developing adverse health consequences. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source]


Oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice: Long-term exposure to low doses

ENVIRONMENTAL TOXICOLOGY, Issue 6 2006
A. Sukenik
Abstract The hepatotoxin cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. The acute toxicity of cylindrospermopsin was well established based on intraperitoneal and oral exposure; however, only a few long-term subacute exposure studies were performed to permit a reliable guideline value for cylindrospermopsin in drinking water. In the study reported herein, female and male mice were exposed to cylindrospermopsin in their drinking water. Cylindrospermopsin-containing, Aphanizomenon ovalisporum (cyanobacterium)-free medium was provided as the only source of drinking water, whereas a control group was given a fresh medium for cyanobacteria as drinking water. Over a period of 42 weeks, experiment groups were exposed to cylindrospermopsin concentration, gradually increased from 100 to 550 ,g L,1 (daily exposure ranged between 10 and 55 ,g kg,1 day,1). Body and organ weights were recorded, and serum and hematology analyses were performed 20 and 42 weeks after the beginning of the experiment. The most pronounced effect of cylindrospermopsin was elevated hematocrit levels in both male and female mice after 16 weeks of exposure to cylindrospermopsin. The observed changes in the hematocrit level were accompanied by deformation of red blood cells, which were changed into acanthocyte. Based on these results, a daily cylindrospermopsin dose of 20 ,g kg,1 day,1 (equivalent to 200 ,g L,1) is proposed as the lowest-observed-adverse-effect level for both male and female mice. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 575,582, 2006. [source]


Toxicity of oral exposure to 2,4,6-trinitrotoluene in the western fence lizard (Sceloporus occidentalis),

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2008
Craig A. McFarland
Abstract Contamination of the soil with the explosive 2,4,6-trinitrotoluene (TNT) has been found at military sites, many of which are habitats used by reptiles. To provide data useful in assessing ecological risk for reptilian species, acute, subacute, and subchronic oral toxicity studies were conducted with the western fence lizard (Sceloporus occidentalis). Oral median lethal dose (LD50) values for TNT in corn oil were 1,038 and 1,579 mg/kg of body weight for male and female lizards, respectively. Overt signs of toxicity included chromaturia, abdominal enlargement, and tremors. A 14-d subacute study followed in which male lizards were orally dosed with TNT (corn oil) at 0, 33, 66, 132, 263, 525, and 1,050 mg/kg of body weight each day. Clinical signs of toxicity, while similar to the LD50 study, were more subtle and noted in lizards receiving TNT amounts of at least 66 mg/kg/d. Chromaturia was an early consistent sign, often preceding the onset of adverse effects. Male lizards in the 60-d subchronic study were dosed at 0, 3, 15, 25, 35, and 45 mg/kg/d with nearly complete survival (>90%) for lizards in all treatments. Changes in food consumption and body weight were observed at 35 and 45 mg/kg/d. Alterations in hematological end points; blood chemistries (albumin, total protein, alkaline phosphatase, calcium); kidney, spleen, and liver weights; and adverse histopathology were observed in lizards exposed at 25 to 45 mg/kg/d. Testosterone concentration, sperm count, and motility were variable between treatments. Although not significant, incidences of hypospermia and testicular atrophy were observed in some individuals. Together, these data suggest a lowest-observed-adverse effect level of 25 mg/kg/d and a no-observed-adverse effect level of 15 mg/kg/d in S. occidentalis. [source]


Dose-related effects following oral exposure of 2,4-dinitrotoluene on the western fence lizard, Sceloporus occidentalis

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2008
Jamie G. Suski
Abstract 2,4-dintitrotoluene (2,4-DNT) is an explosive frequently found in the soil of military installations. Because reptiles can be common on these sites, ecological risk assessments for compounds such as 2,4-DNT could be improved with toxicity data specific to reptiles. Western fence lizards, Sceloporus occidentalis, were used to develop a laboratory toxicity model for reptiles. A hierarchical approach was used; acute to subchronic studies were conducted to provide toxicity data relevant to short- and long-term exposures. First, a modified median lethal dose (LD50) study was conducted on male and female lizards using a stage-wise probit model. The LD50 was 577 mg/kg for female and 380 mg/kg for male lizards. Subsequently, a subacute experiment was conducted to further assess 2,4-DNT toxicity to male lizards and to define exposure levels for a longer term, subchronic study. The subchronic study was conducted for 60 consecutive days; male lizards were exposed to 0, 9, 15, 25, 42, 70 mg/kg/d. Dose-dependent mortality was observed in the three highest dose groups (25, 42, and 70 mg/kg/d); all other animals survived the study duration. Benchmark dose model calculations based on mortality indicated a 5% effect level of 15.8 mg/kg/d. At study termination, a gross necropsy was performed, organ weights were taken, and blood was collected for clinical and hematological analysis. Body weight, kidney weight, food consumption, postdose observations, and blood chemistries all were found to be significantly different from controls at doses above 9 mg/kg/d. Also, preliminary results suggest behavioral observations, and reduced food consumption may be a sensitive indicator of toxicity. The present study indicates Sceloporus occidentalis is suitable for evaluating toxicity of compounds to reptilian species. [source]


A novel model of sensitization and oral tolerance to peanut protein

IMMUNOLOGY, Issue 3 2004
Jessica Strid
Summary The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens. [source]


The infectivity of transmissible spongiform encephalopathy agent at low doses: the importance of phospholipid

JOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2006
P. Gale
Abstract The issue of whether the mechanism of infection is independent or co-operative for low doses of transmissible spongiform encephalopathy (TSE) agent is critical for risk assessment. The susceptibility (and hence ID50) of individuals with the same prion protein (PrP) genotype may vary considerably with a small proportion being very susceptible. Assuming independent action, the incubation period (IP) would continue to increase until the dose is below the ID50 of the most susceptible individuals in the experiment, at which point it would become constant. This may explain the observed increase in IP with decreasing dose below the apparent ID50 in experiments with untreated TSE agent. In contrast, IPs for autoclaved or NaOH-treated TSE agent increase greatly at doses oral exposure to low doses of scrapie is less harmful than a single large exposure, this effect may reflect interference by competition rather than diminished risks due to a co-operative effect, and is of little importance for ,one-off' low-dose environmental exposures. [source]


Effect of Piperine, a Major Component of Black Pepper, on the Intestinal Absorption of Fexofenadine and Its Implication on Food,Drug Interaction

JOURNAL OF FOOD SCIENCE, Issue 3 2010
Ming-Ji Jin
ABSTRACT:, The present study aimed to investigate the effect of piperine, a major component of black pepper, on the oral exposure of fexofenadine in rats. Pharmacokinetic parameters of fexofenadine were determined in rats following an oral (10 mg/kg) or intravenous (5 mg/kg) administration of fexofenadine in the presence and absence of piperine (10 or 20 mg/kg, given orally). Compared to the control group given fexofenadine alone, the combined use of piperine increased the oral exposure (AUC) of fexofenadine by 180% to 190% while there was no significant change in,Cmax and,T1/2 of fexofenadine in rats. The bioavailability of fexofenadine was increased by approximately 2-folds via the concomitant use of piperine. Furthermore,,Tmax tends to be increased which might be attributed to the delayed gastric emptying in the presence of piperine. In contrast, piperine did not alter the intravenous pharmacokinetics of fexofenadine, implying that piperine may increase mainly the gastrointestinal absorption of fexofenadine rather than reducing hepatic extraction. In conclusion, piperine significantly enhanced the oral exposure of fexofenadine in rats likely by the inhibition of P-glycoprotein-mediated cellular efflux during the intestinal absorption, suggesting that the combined use of piperine or piperine-containing diet with fexofenadine may require close monitoring for potential drug,diet interactions. [source]


Mucosal mast cells mediate motor response induced by chronic oral exposure to ovalbumin in the rat gastrointestinal tract

NEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2010
E. Traver
Abstract, We previously demonstrated that oral chronic exposure to ovalbumin (OVA) causes intestinal hypermotility in Sprague-Dawley rats. In this study, the objective was to determine the mechanism of action of OVA and the role of mucosal mast cells in the regulation of motor activity in this model. Rats were orally exposed to OVA during 6 weeks. Intestinal mucosal mast cells (IMMCs) were counted and rat mast cell protease II (RMCPII) measured in duodenum, jejunum, ileum and colon. Anti-OVA IgE, IgG, and IL-4 were measured in serum. Eosinophils and IgE+ cells were counted in jejunum. In an additional study rats were treated with the mast cell stabilizer ketotifen and mast cell number, RMCPII concentration and motor activity in vitro were evaluated. OVA exposed rats showed an increase in mucosal mast cell number and in RMCPII content in small intestine and colon. However, variables of a Th2 type response were not affected by exposure to OVA: (i) neither OVA specific IgE nor IgG were found; (ii) IL-4 did not increase and, (iii) the number of eosinophils and IgE+ cells was identical in the exposed and unexposed groups. These results brought us to hypothesize a possible non-Ig-mediated action of OVA on mast cells. Ketotifen significantly diminished the response to OVA: Ketotifen reduced the number of mast cells and the RMCPII content and blocked increased intestinal contractility. In addition ketotifen modified motor response in both OVA exposed and unexposed animals giving evidence of the importance of mast cells in intestine motor activity driving. [source]


34 Senso-reflexory control of the gastric myoelectrical activity , effect of oral exposure to a sweet or a bitter taste on a multichannel electrogastrogram

NEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2006
M DZIELICKI
Aim:, To examine the effect of sensory stimulation with a sweet or a bitter taste on the interdigestive gastric myoelectrical activity (GMA) in humans. Methods:, Eighteen healthy subjects (10F, 8M) underwent on two separate days four-channel electrogastrographic recordings comprising three consecutive 35 min periods: (i) basal fasted, (ii) a stimulation epoch while a subject was chewing an agar cube soaked with a taste-delivering substance (saccharose for the sweet taste, quinine hydrochloride for the bitter taste), (iii) a post-stimulatory (recovery) epoch. An electrocardiogram was simultaneously registered for the purpose of the heart rate variability (HRV) analysis. Results:, Exposure to the sweet taste brought about an increase in the power of the high frequency (HF: 0.15,0.4 Hz) band of the power spectrum-analyzed HRV data. The bitter taste had no effect on the HRV. During the stimulation and the recovery epoch a statistically significant augmentation in the relative time share of tachy- and bradygastria within the multichannel electrogastrogram was found either with the sweet or the bitter taste. Whereas no any other modifications of the GMA were elicited by the sweet taste, the exposure to the bitter taste resulted in a statistically significant decrease in the relative time share of normogastria, a decline in the dominant frequency and the dominant power of the gastric slow waves, as well as a reduction in the percentage of the slow wave coupling. Conclusions:, (i) Exposure to the sweet taste elicits a vagal arousal expressed by an increase in the HF power, whereas the bitter taste does not affect the equilibrium between the parasympathetic and the sympathetic component of the autonomous nervous system; (ii) The increased relative time contribution of tachy- and bradygastria within the electrogastrogram during both the stimulation and the recovery epoch should be considered an unspecific phenomenon because it accompanied stimulation either with the sweet or the bitter taste; (iii) The inhibitory effect of the bitter taste on the GMA, reflected by a diminution in the dominant frequency and the dominant power of the gastric slow waves, as well as their reduced coupling, may be indicative of an evolutionary archetype of a warning reaction of the human (mammalian) organism towards this taste. [source]


Neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2009
S. Sisó
Background: It is generally believed that after oral exposure to transmissible spongiform encephalopathy (TSE) agents, neuroinvasion occurs via the enteric nervous system (ENS) and the autonomic nervous system. As a result, the dorsal motor nucleus of the vagus nerve is the initial point of disease-associated prion protein (PrPd) accumulation in the brain. Hypothesis and aim: If direct ENS invasion following oral infection results in an early and specific brain targeting for PrPd accumulation, such topographical distribution could be different when other routes of infection were used, highlighting distinct routes for neuroinvasion. Methods: An immunohistochemical study has been conducted on the brain of 67 preclinically infected sheep exposed to natural scrapie or to experimental TSE infection by various routes. Results: Initial PrPd accumulation consistently occurred in the dorsal motor nucleus of the vagus nerve followed by the hypothalamus, regardless of the breed of sheep, PrP genotype, TSE source and, notably, route of infection; these factors did not appear to affect the topographical progression of PrPd deposition in the brain either. Moreover, the early and consistent appearance of PrPd aggregates in the circumventricular organs, where the blood,brain barrier is absent, suggests that these organs can provide a portal for entry of prions when infectivity is present in blood. Conclusions: The haematogenous route, therefore, can represent a parallel or alternative pathway of neuroinvasion to ascending infection via the ENS/autonomic nervous system. [source]


Migration of alkylbenzenes from packaging into food and Tenax®

PACKAGING TECHNOLOGY AND SCIENCE, Issue 2 2001
B. Aurela
Abstract Alkylbenzenes (alkyl chain C10,C13) are used as solvent components in certain offset printing inks. Alkylbenzenes were identified from 10 out of 15 samples of offset-printed food packaging made of board. Printed hamburger collars intended for hamburger restaurants had exceptionally high contents of alkylbenzenes (70,500,mg/kg). Most of the collars had varnish on both the printed surface and the non-printed food contact surface. Migration of alkylbenzenes from the hamburger collar into a roll was 2,mg/kg. In another test, in which Tenax® was used as simulant, the effect of a varnish layer on the food contact surface was studied. It was found that the varnish layer reduced migration by about 70%. Tests with Tenax® as a food simulant resulted in higher migration than in tests with rolls. The European Commission has published a risk assessment report on alkylbenzenes. The report concludes that there is no need for further testing or for risk reduction measures beyond those which are currently applied. However, consumer exposure was calculated without taking into account the possibility of oral exposure to alkylbenzenes migrating from food packagings. The migration of alkylbenzenes thus merits further study. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Influence of dietary 2,4,6-trinitrotoluene exposure in the northern bobwhite (Colinus virginianus)

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2002
Robert M. Gogal Jr.
Abstract The risk to wildlife from exposure to the explosive, 2,4,6-trinitrotoluene (TNT) has been a concern at numerous military installations where it has been found in the soil. To date, no published data are available describing effects of TNT exposure in an avian species. Subchronic dietary exposure to TNT was therefore evaluated in a species of management concern at military installations, the northern bobwhite (Colinus virginianus). Adult male and female quail (n = 5/sex/dose) were given commercial feed containing 3,000, 1,500, 750, and 100 mg/kg TNT for 90 d following the determination of an acute lethal dose and a 14-d range finding study. Dietary TNT intake caused a dose-dependent decrease in total red blood cell counts, packed cell volume, total plasma protein, blood prolymphocytes, and blood lymphocytes. An increased trend in late apoptotic/necrotic blood leukocytic cells was also observed in TNT-exposed birds, as was hemosiderosis in the liver. With the exception of hemosiderosis, these trends were statistically significant yet of questionable biological significance. Since treatment-related responses in this preliminary study were variable, a conservative interpretation is suggested. However, since these treatments had concentrations that were a log-fold or more than doses in similar studies using mammals, these data suggest that northern bobwhite are less sensitive to oral exposures of TNT than mammals. [source]